Evidence map›Paper›PMID 25263804›Full record

ArticleGastroenterology2015

Epigenetic regulation of genes that modulate chronic stress-induced visceral pain in the peripheral nervous system.

Shuangsong Hong, Gen Zheng, John W Wiley

Open access · greenAbstract read
In one paragraph

Article in Gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed
11.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

86 citing papers in PubMed, 149 citations in OpenAlex.

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  12. Critical Windows: Exploring the Association Between Perinatal Trauma, Epigenetics, and Chronic Pain.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024
    Review
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  16. Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024
    Review
  17. Article
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  19. Article
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26 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Shuangsong HongDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan. Electronic address: hongss@med.umich.edu.
Gen ZhengDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
John W WileyDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
University of Michigan–Ann Arbor · US

Funding

University of Michigan Center for Gastrointestinal ResearchP30DK034933 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OWYANG, CHUNG · 1986 to 2021
$22.5M
Chronic Stress and Abdominal Pain: Novel MechanismsR01DK098205 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WILEY, JOHN W · 2013 to 2017
$1.7M
Stress and Visceral Hyperalgesia: Epigenetic MechanismsR56DK093631 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WILEY, JOHN W · 2012 to 2012
$334k
NIDDK NIH HHS 5P30DK034933NIDDK NIH HHS P30 DK034933NIDDK NIH HHS R01 DK098205NIDDK NIH HHS R01DK098205NIDDK NIH HHS R56 DK093631
6 · The paper itself

Abstract

BACKGROUND &

aimsChronic stress alters the hypothalamic-pituitary-adrenal axis, increases gut motility, and increases the perception of visceral pain. We investigated whether epigenetic mechanisms regulate chronic stress-induced visceral pain in the peripheral nervous systems of rats.

methodsMale rats were subjected to 1 hour of water avoidance stress each day, or given daily subcutaneous injections of corticosterone, for 10 consecutive days. L4-L5 and L6-S2 dorsal root ganglia (DRG) were collected and compared between stressed and control rats (placed for 1 hour each day in a tank without water). Levels of cannabinoid receptor 1 (CNR1), DNA (cytosine-5-)-methyltransferase 1 (DNMT1), transient receptor potential vanilloid type 1 (TRPV1), and EP300 were knocked down in DRG neurons in situ with small interfering RNAs. We measured DNA methylation and histone acetylation at genes encoding the glucocorticoid receptor (NR3C1), CNR1, and TRPV1. Visceral pain was measured in response to colorectal distention.

resultsChronic stress was associated with increased methylation of the Nr3c1 promoter and reduced expression of this gene in L6-S2, but not L4-L5, DRGs. Stress also was associated with up-regulation in DNMT1-associated methylation of the Cnr1 promoter and down-regulation of glucocorticoid-receptor-mediated expression of CNR1 in L6-S2, but not L4-L5, DRGs. Concurrently, chronic stress increased expression of the histone acetyltransferase EP300 and increased histone acetylation at the Trpv1 promoter and expression of the TRPV1 receptor in L6-S2 DRG neurons. Knockdown of DNMT1 and EP300 in L6-S2 DRG neurons of rats reduced DNA methylation and histone acetylation, respectively, and prevented chronic stress-induced increases in visceral pain.

conclusionsChronic stress increases DNA methylation and histone acetylation of genes that regulate visceral pain sensation in the peripheral nervous system of rats. Blocking epigenetic regulatory pathways in specific regions of the spinal cord might be developed to treat patients with chronic abdominal pain.

Indexed as

Epigenesis, GeneticAbdominal PainAcetylationAnimalsChronic DiseaseDisease Models, AnimalDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA MethylationE1A-Associated p300 ProteinGanglia, SpinalGene Expression RegulationHistonesHyperalgesiaMalePain MeasurementCnr1 protein, ratDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDnmt1 protein, ratE1A-Associated p300 ProteinEp300 protein, ratHistonesNR3C1 protein, ratReceptor, Cannabinoid, CB1Receptors, GlucocorticoidTrpv1 protein, ratTRPV Cation ChannelsEpigenetic ModificationHPAPain SensitivityVisceral Hyperalgesia

Identifiers

PMID25263804
PMCPMC4274248
OpenAlexW2167410483

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.